ABCC7 p.Asn418Ser
| ClinVar: |
c.1253A>G
,
p.Asn418Ser
?
, not provided
c.1254T>C , p.Asn418= N , Benign |
| CF databases: |
c.1253A>G
,
p.Asn418Ser
(CFTR1)
?
, A novel mutation was identified by SSCP and direct sequencing. The nucleotide change A->G at position 1385 in exon 9 resulting in a replacement of a asparagine by a serine at position 418 (N418S). This mutation was found in two unrelated CF alleles. Both patients are compund heterozygous for [delta]F508.
|
| Predicted by SNAP2: | A: N (87%), C: N (66%), D: N (97%), E: N (93%), F: N (57%), G: N (93%), H: N (87%), I: N (78%), K: N (87%), L: N (78%), M: N (82%), P: N (82%), Q: N (93%), R: N (82%), S: N (97%), T: N (97%), V: N (82%), W: N (57%), Y: N (78%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] A combined analysis of the cystic fibrosis transme... Mol Biol Evol. 2001 Sep;18(9):1771-88. Chen JM, Cutler C, Jacques C, Boeuf G, Denamur E, Lecointre G, Mercier B, Cramb G, Ferec C
A combined analysis of the cystic fibrosis transmembrane conductance regulator: implications for structure and disease models.
Mol Biol Evol. 2001 Sep;18(9):1771-88., [PMID:11504857]
Abstract [show]
Over the past decade, nearly 1,000 variants have been identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in classic and atypical cystic fibrosis (CF) patients worldwide, and an enormous wealth of information concerning the structure and function of the protein has also been accumulated. These data, if evaluated together in a sequence comparison of all currently available CFTR homologs, are likely to refine the global structure-function relationship of the protein, which will, in turn, facilitate interpretation of the identified mutations in the gene. Based on such a combined analysis, we had recently defined a "functional R domain" of the CFTR protein. First, presenting two full-length cDNA sequences (termed sCFTR-I and sCFTR-II) from the Atlantic salmon (Salmo salar) and an additional partial coding sequence from the eastern gray kangaroo (Macropus giganteus), this study went further to refine the boundaries of the two nucleotide-binding domains (NBDs) and the COOH-terminal tail (C-tail), wherein NBD1 was defined as going from P439 to G646, NBD2 as going from A1225 to E1417, and the C-tail as going from E1418 to L1480. This approach also provided further insights into the differential roles of the two halves of CFTR and highlighted several well-conserved motifs that may be involved in inter- or intramolecular interactions. Moreover, a serious concern that a certain fraction of missense mutations identified in the CFTR gene may not have functional consequences was raised. Finally, phylogenetic analysis of all the full-length CFTR amino acid sequences and an extended set of exon 13--coding nucleotide sequences reinforced the idea that the rabbit may represent a better CF model than the mouse and strengthened the assertion that a long-branch attraction artifact separates the murine rodents from the rabbit and the guinea pig, the other Glires.
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No. Sentence Comment
591 Similarly, the missense mutations occurring in evolutionarily divergent regions, for example, N418S, G424S, Q890R, and K1177R, may also represent neutral polymorphisms.
X
ABCC7 p.Asn418Ser 11504857:591:94
status: NEW[hide] Missense, nonsense, and neutral mutations define j... J Biol Chem. 2003 Jul 18;278(29):26580-8. Epub 2003 May 5. Pagani F, Buratti E, Stuani C, Baralle FE
Missense, nonsense, and neutral mutations define juxtaposed regulatory elements of splicing in cystic fibrosis transmembrane regulator exon 9.
J Biol Chem. 2003 Jul 18;278(29):26580-8. Epub 2003 May 5., 2003-07-18 [PMID:12732620]
Abstract [show]
Exonic sequence variations may induce exon inclusion or exclusion from the mature mRNA by disrupting exonic regulatory elements and/or by affecting a nuclear reading frame scanning mechanism. We have carried out a systematic study of the effect on cystic fibrosis transmembrane regulator exon 9 splicing of natural and site-directed sequence mutations. We have observed that changes in the splicing pattern were not related to the creation of premature termination codons, a fact that indicates the lack of a significant nuclear check of the reading frame in this system. In addition, the splice pattern could not be predicted by available Ser/Arg protein matrices score analysis. An extensive site-directed mutagenesis of the 3' portion of the exon has identified two juxtaposed splicing enhancer and silencer elements. The study of double mutants at these regulatory elements showed a complex regulatory activity. For example, one natural mutation (146C) enhances exon inclusion and overrides all of the downstream silencing mutations except for a C to G transversion (155G). This unusual effect is explained by the creation of a specific binding site for the inhibitory splicing factor hnRNPH. In fact, on the double mutant 146C-155G, the silencing effect is dominant. These results indicate a strict dependence between the two juxtaposed enhancer and silencer sequences and show that many point mutations in these elements cause changes in splicing efficiency by different mechanisms.
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No. Sentence Comment
83 Four of the natural substitutions, C31T (Q414X), G61A (G424S), T122G (I444S), and C155A (A455E), significantly decreased exon 9 inclusion to 48, 30, 40, and 16%, respectively, whereas only a modest decrease was evident for N418S.
X
ABCC7 p.Asn418Ser 12732620:83:223
status: NEW